tbuckley/cabot-search huggingface dataset:
Updated Analysis of NEJ009: Gefitinib-Alone Versus Gefitinib Plus Chemotherapy for Non–Small-Cell Lung Cancer With Mutated <i>EGFR</i>
Authors: Eisaku Miyauchi, Satoshi Morita, Atsushi Nakamura, Yukio Hosomi, Kana Watanabe, Satoshi Ikeda, Masahiro Seike, Yuka Fujita, Koichi Minato, Ryo Ko, Toshiyuki Harada, Koichi Hagiwara, Kunihiko Kobayashi, Toshihiro Nukiwa, Akira Inoue
Journal: Journal of Clinical Oncology (2022)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In a randomized, open-label, phase III NEJ009 study, gefitinib plus chemotherapy significantly improved progression-free survival (PFS) and overall survival (OS) compared with gefitinib-alone in patients with untreated non-small-cell lung cancer harboring mutations in epidermal growth factor receptor. Herein, we report the updated survival outcome and long-term tolerability. Patients were randomly assigned to gefitinib (gefitinib 250 mg orally, once daily) and gefitinib combined with carboplatin plus pemetrexed (GCP in a 3-week cycle for six cycles followed by concurrent gefitinib and pemetrexed maintenance) groups. At the data cutoff (May 22, 2020), GCP demonstrated significantly better PFS2 (hazard ratio, 0.77; 95% CI, 0.62 to 0.97; P = .027) than gefitinib. However, the updated median OS was 38.5 months (95% CI, 31.1 to 47.1) and 49.0 months (95% CI, 41.8 to 56.7) in the gefitinib and GCP groups, respectively (hazard ratio, 0.82; 95% CI, 0.64 to 1.06; P = .127). The OS in both groups was similar for the overall patient population. No severe adverse events occurred since the first report. This updated analysis revealed that the GCP regimen improved PFS and PFS2 with an acceptable safety profile compared with gefitinib-alone. GCP is more efficient than gefitinib monotherapy as a first-line treatment for non-small-cell lung cancer with epidermal growth factor receptor mutations.
A Randomized, Double-Blind, Biomarker-Selected, Phase II Clinical Trial of Maintenance Poly ADP-Ribose Polymerase Inhibition With Rucaparib Following Chemotherapy for Metastatic Urothelial Carcinoma
Authors: Simon J. Crabb, Syed Hussain, Eileen Soulis, Samantha Hinsley, Laura Dempsey, Avril Trevethan, YeePei Song, Jim Barber, John Frew, Joanna Gale, Guy Faust, Susannah Brock, Ursula McGovern, Omi Parikh, Deborah Enting, Santhanam Sundar, Gihan Ratnayake, Kathryn Lees, Alison J. Birtle, Thomas Powles, Robert J. Jones
Journal: Journal of Clinical Oncology (2022)

A DNA repair deficiency (DRD) phenotype exists within a subset of metastatic urothelial carcinomas (mUC) predicting benefit from platinum-based chemotherapy. We tested switch maintenance therapy with the poly ADP-ribose polymerase inhibitor rucaparib, following chemotherapy, for DRD biomarker-positive mUC.
Intensity-Modulated Radiation Therapy Reduces Patient-Reported Chronic Toxicity Compared With Conventional Pelvic Radiation Therapy: Updated Results of a Phase III Trial
Authors: Anamaria R. Yeung, Snehal Deshmukh, Ann H. Klopp, Karen M. Gil, Lari Wenzel, Shannon N. Westin, Andre A. Konski, David K. Gaffney, William Small, J. Spencer Thompson, Desiree E. Doncals, Guilherme H.C. Cantuaria, David P. D'Souza, Amy Chang, Vijayananda Kundapur, Dasarahally S. Mohan, Michael L. Haas, Yong Bae Kim, Catherine L. Ferguson, Stephanie L. Pugh, Lisa A. Kachnic, Deborah W. Bruner
Journal: Journal of Clinical Oncology (2022)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The purpose of this update was to determine differences in patient-reported chronic toxicity and disease outcomes with intensity-modulated radiation therapy (IMRT) compared with conventional pelvic radiation. Patients with cervical and endometrial cancers who received postoperative pelvic radiation were randomly assigned to conventional radiation therapy (CRT) or IMRT. Toxicity and quality of life were assessed using Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domains, and Functional Assessment of Cancer Therapy-General. Between 2012 and 2015, 279 eligible patients were enrolled to the study with a median follow-up of 37.8 months. There were no differences in overall survival (P = .53), disease-free survival (P = .21), or locoregional failure (P = .81). One year after RT, patients in the CRT arm experienced more high-level diarrhea frequency (5.8% IMRT v 15.1% CRT, P = .042) and a greater number had to take antidiarrheal medication two or more times a day (1.2% IMRT v 8.6% CRT, P = .036). At 3 years, women in the CRT arm reported a decline in urinary function, whereas the IMRT arm continued to improve (mean change in EPIC urinary score = 0.5, standard deviation = 13.0, IMRT v -6.0, standard deviation = 14.3, CRT, P = .005). In conclusion, IMRT reduces patient-reported chronic GI and urinary toxicity with no difference in treatment efficacy at 3 years.
Cascade Testing for Hereditary Cancer Syndromes: Should We Move Toward Direct Relative Contact? A Systematic Review and Meta-Analysis
Authors: Melissa K. Frey, Muhammad Danyal Ahsan, Hannah Bergeron, Jenny Lin, Xuan Li, Rana K. Fowlkes, Priyanka Narayan, Roni Nitecki, Jose Alejandro Rauh-Hain, Haley A. Moss, Becky Baltich Nelson, Charlene Thomas, Paul J. Christos, Jada G. Hamilton, Eloise Chapman-Davis, Evelyn Cantillo, Kevin Holcomb, Allison W. Kurian, Steven Lipkin, Kenneth Offit, Ravi N. Sharaf
Journal: Journal of Clinical Oncology (2022)

Evidence-based guidelines recommend cascade genetic counseling and testing for hereditary cancer syndromes, providing relatives the opportunity for early detection and prevention of cancer. The current standard is for patients to contact and encourage relatives (patient-mediated contact) to undergo counseling and testing. Direct relative contact by the medical team or testing laboratory has shown promise but is complicated by privacy laws and lack of infrastructure. We sought to compare outcomes associated with patient-mediated and direct relative contact for hereditary cancer cascade genetic counseling and testing in the first meta-analysis on this topic.We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO No.: CRD42020134276). We searched key electronic databases to identify studies evaluating hereditary cancer cascade testing. Eligible trials were subjected to meta-analysis.Eighty-seven studies met inclusion criteria. Among relatives included in the meta-analysis, 48% (95% CI, 38 to 58) underwent cascade genetic counseling and 41% (95% CI, 34 to 48) cascade genetic testing. Compared with the patient-mediated approach, direct relative contact resulted in significantly higher uptake of genetic counseling for all relatives (63% [95% CI, 49 to 75] v 35% [95% CI, 24 to 48]) and genetic testing for first-degree relatives (62% [95% CI, 49 to 73] v 40% [95% CI, 32 to 48]). Methods of direct contact included telephone calls, letters, and e-mails; respective rates of genetic testing completion were 61% (95% CI, 51 to 70), 48% (95% CI, 37 to 59), and 48% (95% CI, 45 to 50).Most relatives at risk for hereditary cancer do not undergo cascade genetic counseling and testing, forgoing potentially life-saving medical interventions. Compared with patient-mediated contact, direct relative contact increased rates of cascade genetic counseling and testing, arguing for a shift in the care delivery paradigm, to be confirmed by randomized controlled trials.
Advancements in redox-sensitive micelles as nanotheranostics: A new horizon in cancer management
Authors: Anupama Sikder, Ganesh Vambhurkar, Etikala Amulya, Deepkumar Bagasariya, Paras Famta, Saurabh Shah, Dharmendra Kumar Khatri, Shashi Bala Singh, V R Sinha, Saurabh Srivastava
Journal: Journal of Controlled Release (2022)
Use of genetically modified lactic acid bacteria and bifidobacteria as live delivery vectors for human and animal health
Authors: Romina Levit, Naima G. Cortes-Perez, Alejandra de Moreno de Leblanc, Jade Loiseau, Anne Aucouturier, Philippe Langella, Jean Guy LeBlanc, Luis G. Bermúdez-Humarán
Journal: Gut Microbes (2022)

There is now strong evidence to support the interest in using lactic acid bacteria (LAB)in particular, strains of lactococci and lactobacilli, as well as bifidobacteria, for the development of new live vectors for human and animal health purposes. LAB are Gram-positive bacteria that have been used for millennia in the production of fermented foods. In addition, numerous studies have shown that genetically modified LAB and bifodobacteria can induce a systemic and mucosal immune response against certain antigens when administered mucosally. They are therefore good candidates for the development of new mucosal delivery strategies and are attractive alternatives to vaccines based on attenuated pathogenic bacteria whose use presents health risks. This article reviews the most recent research and advances in the use of LAB and bifidobacteria as live delivery vectors for human and animal health.
VWF-targeted thrombolysis to overcome rh-tPA resistance in experimental murine ischemic stroke models
Authors: Marc V. A. van Moorsel, Steven de Maat, Kristof Vercruysse, Esther M. van Leeuwen, Charlène Jacqmarcq, Thomas Bonnard, Denis Vivien, H. Bart van der Worp, Rick M. Dijkhuizen, Coen Maas
Journal: Blood (2022)
A model of painful vaso-occlusive crisis in mice with sickle cell disease
Authors: Iryna I. Khasabova, Joseph Juliette, Victoria M. Rogness, Sergey G. Khasabov, Mikhail Y. Golovko, Svetlana A. Golovko, Stacy Kiven, Kalpna Gupta, John D. Belcher, Gregory M. Vercellotti, Virginia S. Seybold, Donald A. Simone
Journal: Blood (2022)

In order to better understand mechanisms underlying acute pain during vaso-occlusive crises (VOCs) in patients with sickle cell disease, Khasabova et al report on a clinically relevant model in mice where VOC is stimulated by exposure to cold. Cold exposure produces robust hyperalgesia, stasis, hypoxia, elevated heart rate, and increased levels of the endocannabinoid 2-AG and its synthesizing enzyme, DAGLβ, in plasma and blood cells, respectively. Blocking DAGLβ prevents the development of hyperalgesia. Collectively, these data point to 2-AG signaling as a targetable mediator of VOC pain.
Pretransplant <i>FLT3</i>-ITD MRD assessed by high-sensitivity PCR-NGS determines posttransplant clinical outcome
Authors: Sun Loo, Richard Dillon, Adam Ivey, Natasha S. Anstee, Jad Othman, Ing Soo Tiong, Nicola Potter, Jelena Jovanovic, Manohursingh Runglall, Chyn Chua Chong, Ashish Bajel, David Ritchie, Kelli Gray, Zhi Han Yeoh, Michelle McBean, Amanda Gilkes, Ian Thomas, Sean Johnson, Nigel H. Russell, Andrew H. Wei
Journal: Blood (2022)
Aberrant MYCN expression drives oncogenic hijacking of EZH2 as a transcriptional activator in peripheral T-cell lymphoma
Authors: Marlies Vanden Bempt, Koen Debackere, Sofie Demeyer, Quentin Van Thillo, Nienke Meeuws, Cristina Prieto, Sarah Provost, Nicole Mentens, Kris Jacobs, Olga Gielen, David Nittner, Seishi Ogawa, Keisuke Kataoka, Carlos Graux, Thomas Tousseyn, Jan Cools, Daan Dierickx
Journal: Blood (2022)

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of hematological cancers arising from the malignant transformation of mature T cells. In a cohort of 28 PTCL cases, we identified recurrent overexpression of MYCN, a member of the MYC family of oncogenic transcription factors. Approximately half of all PTCL cases was characterized by a MYC expression signature. Inducible expression of MYCN in lymphoid cells in a mouse model caused T-cell lymphoma that recapitulated human PTCL with an MYC expression signature. Integration of mouse and human expression data identified EZH2 as a key downstream target of MYCN. Remarkably, EZH2 was found to be an essential cofactor for the transcriptional activation of the MYCN-driven gene expression program, which was independent of methyltransferase activity but dependent on phosphorylation by CDK1. MYCN-driven T-cell lymphoma was sensitive to EZH2 degradation or CDK1 inhibition, which displayed synergy with US Food and Drug Administration-approved histone deacetylase (HDAC) inhibitors.
Dual Diagnostic Role of 123I-MIBG Scintigraphy in Inverted Takotsubo Cardiomyopathy
Authors: Olivier Humbert
Journal: Clinical Nuclear Medicine (2016)

Imaging Department, CHU Nuclear Medicine Department Centre GF Leclerc and Université de Bourgogne Franche-Comté UMR CNRS 6306 Dijon, France [email protected] Conflicts of interest and sources of funding: none declared.
Linking the effect of localised pitting corrosion with mechanical integrity of a rare earth magnesium alloy for implant use
Authors: Kerstin van Gaalen, Conall Quinn, Felix Benn, Peter E. McHugh, Alexander Kopp, Ted J. Vaughan
Journal: Bioactive Materials (2022)

This study presents a computational framework that investigates the effect of localised surface-based corrosion on the mechanical performance of a magnesium-based alloy. A finite element-based phenomenological corrosion model was used to generate a wide range of corrosion profiles, with subsequent uniaxial tensile test simulations to predict the mechanical response to failure. The python-based detection framework PitScan provides detailed quantification of the spatial phenomenological features of corrosion, including a full geometric tracking of corroding surface. Through this approach, this study is the first to quantitatively demonstrate that a surface-based non-uniform corrosion model can capture both the geometrical and mechanical features of a magnesium alloy undergoing corrosion by comparing to experimental data. Using this verified corrosion modelling approach, a wide range of corrosion scenarios was evaluated and enabled quantitative relationships to be established between the mechanical integrity and key phenomenological corrosion features. In particular, we demonstrated that the minimal cross-sectional area parameter was the strongest predictor of the remaining mechanical strength (R2 = 0.98), with this relationship being independent of the severity or spatial features of localised surface corrosion. Interestingly, our analysis demonstrated that parameters described in ASTM G46-94 showed weaker correlations to the mechanical integrity of corroding specimens, compared to parameters determined by Pitscan. This study establishes new mechanistic insight into the performance of the magnesium-based materials undergoing corrosion.
Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the RANO <i>resect</i> group
Authors: Philipp Karschnia, Jacob S Young, Antonio Dono, Levin Häni, Tommaso Sciortino, Francesco Bruno, Stephanie T Juenger, Nico Teske, Ramin A Morshed, Alexander F Haddad, Yalan Zhang, Sophia Stoecklein, Michael Weller, Michael A Vogelbaum, Juergen Beck, Nitin Tandon, Shawn Hervey-Jumper, Annette M Molinaro, Roberta Rudà, Lorenzo Bello, Oliver Schnell, Yoshua Esquenazi, Maximilian I Ruge, Stefan J Grau, Mitchel S Berger, Susan M Chang, Martin van den Bent, Joerg-Christian Tonn
Journal: Neuro-Oncology (2022)

Terminology to describe extent of resection in glioblastoma is inconsistent across clinical trials. A surgical classification system was previously proposed based upon residual contrast-enhancing (CE) tumor. We aimed to (1) explore the prognostic utility of the classification system and (2) define how much removed non-CE tumor translates into a survival benefit.The international RANO resect group retrospectively searched previously compiled databases from 7 neuro-oncological centers in the USA and Europe for patients with newly diagnosed glioblastoma per WHO 2021 classification. Clinical and volumetric information from pre- and postoperative MRI were collected.We collected 1,008 patients with newly diagnosed IDHwt glioblastoma. 744 IDHwt glioblastomas were treated with radiochemotherapy per EORTC-26981/22981 (TMZ/RT→TMZ) following surgery. Among these homogenously treated patients, lower absolute residual tumor volumes (in cm3) were favorably associated with outcome: patients with "maximal CE resection" (class 2) had superior outcome compared to patients with "submaximal CE resection" (class 3) or "biopsy" (class 4). Extensive resection of non-CE tumor (≤5 cm3 residual non-CE tumor) was associated with better survival among patients with complete CE resection, thus defining class 1 ("supramaximal CE resection"). The prognostic value of the resection classes was retained on multivariate analysis when adjusting for molecular and clinical markers.The proposed "RANO categories for extent of resection in glioblastoma" are highly prognostic and may serve for stratification within clinical trials. Removal of non-CE tumor beyond the CE tumor borders may translate into additional survival benefit, providing a rationale to explicitly denominate such "supramaximal CE resection."
Answer
Journal: Thorax (2008)

From the question on page 620.Lobectomy was performed.The cut surface revealed a poorly circumscribed yellow to white firm area 9.066.566.0 cm which included a white necrotic tumorous lesion measuring 6.065.565.0 cm (fig 1A).A feeding artery, 0.3 cm in diameter, from the descending thoracic aorta was seen nearby.Pathological examination of the consolidated mass was consistent with an intralobar sequestration accompanied by obstructive pneumonia with dense infiltrations of lymphoplasma cells, foamy histiocytes and fibroblasts.The tumour demonstrated an adenocarcinoma admixed with spindle cells and pleomorphic cells (fig 1B) which showed cytokeratin and vimentin coexpression.The diagnosis of a pleomorphic carcinoma arising in an intralobar sequestration with frequent tumour emboli and regional lymph node metastases was made.Adjuvant chemotherapy with two cycles of navelbine was administered but was withdrawn owing to neutropenia.Hoarseness, exertional dyspnoea, productive cough and choking developed progressively.The patient was readmitted 3 months after surgery because of total occlusion of the left main bronchus, left upper lobe collapse, vocal cord palsy and right fourth rib metastasis with pathological fracture.Although a stent was inserted in the left main bronchus as palliative treatment, the patient died of right lung pneumonia with septic shock.Pulmonary sequestration is rarely associated with lung cancer. 1 2 In the previously reported four cases, three cases of squamous cell carcinoma and one case of adenocarcinoma developed within the sequestered lung.The relationship between pulmonary sequestration and lung cancer is uncertain.Complete resection of the malignant lesion with the sequestered lung was performed, and all the patients tolerated the surgery well.Pleomorphic carcinoma, also known as monophasic sarcomatoid carcinoma, is a rare and aggressive pulmonary malignancy.This type of tumour shows concurrent presence of malignant epithelial and homologous sarcomatoid cell components by coexpressing cytokeratin and vimentin in various degrees.Men are affected far more frequently than women (13:3) and the disease is strongly associated with smoking.All of the patients succumbed to early distant metastases (range 2 weeks to 5 months).The prognosis is poor with a median survival of 3 months even when early-stage disease was diagnosed and resected. 3 4 To our knowledge, this is the first case of a pleomorphic carcinoma arising in intralobar sequestration.Preoperative diagnosis of such a case is difficult.When pleomorphic carcinoma is
POS0282 UPDATE ON COMPARATIVE CARDIOVASCULAR SAFETY OF FEBUXOSTAT VERSUS ALLOPURINOL AMONG PATIENTS WITH GOUT
Authors: A. Shin, Y. J. Ha, Y. J. Lee, E. B. Lee, E. H. Kang
Journal: Annals of the Rheumatic Diseases (2022)

Background Gout is associated with an increased risk of cardiovascular (CV) disease. Objectives To update comparative CV safety of febuxostat versus allopurinol among patients with gout Methods Using the 2011-2019 Korea National Health Insurance database, we conducted a cohort study comparing gout patients initiating febuxostat versus allopurinol, with study participants matched on a propensity score (PS) for&gt;60 covariates at a 1:1 ratio. The primary outcome was composite CV outcome of myocardial infarction, coronary revascularization, and stroke. Secondary outcomes were CV and all-cause mortalities in addition to individual components of the primary outcome. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), comparing febuxostat versus allopurinol initiators. Results We included 160,930 febuxostat users PS-matched on 160,930 allopurinol users (mean age 59.3 years, 79.6% male). During a mean follow-up of 250 days, the incidence rate of the primary outcome was 2.27 and 2.06 per 100 person-years for allopurinol and febuxostat users respectively, with the PS-matched HR [95% CI] of 1.03 [0.95-1.12]. Analysis on secondary outcomes also showed a similar result except for all-cause mortality with a significantly reduced risk among febuxostat users with a PS-matched HR [95% CI] of 0.84 [0.78-0.91] (Table 1). Table 1. Comparative cardiovascular safety between febuxostat and allopurinol Febuxostat N = 160,930 Allopurinol (Ref) N= 160,930 HR (95% CI) Events PY a IR [95% CI] Events PY a IR(95% CI] Composite CV endpoint 2635 128,193 2.06 [1.98-2.13] 2,099 92,512 2.27 [2.17-2.37] 1.03 [0.95-1.12] MI 468 129,873 0.36 [0.33-0.39] 341 93,808 0.36 [0.33-0.40] 1.13 [0.91-1.39] Coronary revascularization 1085 129,233 0.84 [0.79-0.89] 856 93,293 0.92 [0.86-0.98] 1.10 [0.96-1.26] Stroke or TIA 1490 129,163 1.15 [1.10-1.21] 1,187 93,252 1.27 [1.20-1.35] 0.99 [0.90-1.10] Death 2558 130,176 1.97 [1.89-2.04] 2,201 94,007 2.34 [2.24-2.44] 0.84 [0.78-0.91] a IR is per 100 person-years. IR=incidence rate, HR=hazard ratio, CI=confidence interval, MI=myocardial infarction, PY=person-years, TIA=transient ischemic attack Conclusion This large population-based cohort study showed a similar CV safety profile between febuxostat and allopurinol users but found a 16% reduced all-cause mortality among febuxostat users compared to allopurinol, primarily derived from non-CV death reduction. Disclosure of Interests None declared